Tumor Suppressive Activity of High Phenolic Sorghum Brans in Colon Cancer Mouse Model and Proposed Mechanisms

Abstract Objectives Colon cancer occupy third rank in the United States and its incidence is inversely associated with high consumption of plant-based diet including whole grains. Sorghum is one of broadly cultivated crops and the bran of sorghum contains high content of bioactive compounds including polyphenols. The current study was designed to examine if different type of high phenolic sorghum brans (PI570481, SC84 and Sumac) suppress tumor formation in genetic colon cancer mouse model and elucidate related biochemical and molecular mechanisms using human colon cancer cells. Methods Fifty-three ApcMin/+ mice (4-week old male and female) were assigned and provided with one of following diets; 1) control (n = 11), 2) low dose of PI570481 (7.5% w/w) (n = 11), 3) high dose of PI570481 (15% w/w) (n = 11), 4) SC84 (15% w/w) (n = 10) and 5) Sumac (15% w/w) (n = 10) for 6 weeks. All mice were treated with 2% dextran sodium sulfate for one week in drinking water at 5 weeks of age. The number and size of tumor were measured from the large intestine. For in vitro study, human colon cancer cell lines were treated with different doses (0, 1.25 and 2.5 mg/mL) of high phenolic sorghum bran extracts (PI570481, SC84 and Sumac). Transcriptional activity of β-catenin was analyzed by measuring luciferase activity of reporter gene (Top and Fop flash). Gene expression was analyzed by Western blot using specific antibodies. Results Feeding three different types of high phenolic sorghum brans (PI570481, SC84 and Sumac) to ApcMin/+ mice for 6 weeks did not change body weight and cause any toxicity. The tumor number and tumor load in the large intestine were significantly decreased in the mice treated with three types of high phenolic sorghum brans. Regarding mechanisms, treatment of high phenolic sorghum bran extracts repressed transcriptional activity of β-catenin and IGF-1-stimulated phosphorylation of Akt in human colon cancer cells. Conclusions Our data propose a potential use of high phenolic sorghum brans as diets for the prevention of human colon cancer. Funding Sources Cooperative Agreement from USDA-ARS to University of Maryland (S-HL).